不可逆的APC ((Cdh1) 不活化是细胞循环进入无回归点的基础
Steven D Cappell1, Mingyu Chung1, Ariel Jaimovich1
1Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Cell
|July 2, 2016
概括
细胞循环承诺对于癌症至关重要,它是由亚纳相促进复合体/循环体 (APC/Cdh1) 失活决定的. 这种不可逆转的开关防止细胞在DNA复制开始后恢复静止状态.
科学领域:
- 细胞生物学
- 分子生物学
- 生物化学
背景情况:
- 在DNA复制和分裂之前,细胞增殖需要一个承诺点.
- 视网母细胞瘤 (Rb) 蛋白酸化是这一决定的建议媒介.
- 细胞循环的失调有助于癌症和退行性疾病.
研究的目的:
- 确定作为细胞循环进入不可逆转的承诺点的分子机制.
- 调查亚相促进复合体/循环体 (APC/Cdh1) 在细胞循环承诺中的作用.
- 为了确定细胞应激反应的时间和可逆性.
主要方法:
- 细胞周期分析
- 蛋白质化试验
- 对APC/Cdh1活动的分析
- 细胞应激诱导实验
主要成果:
- APC/Cdh1 失活是细胞循环进入不可逆转的终点.
- APC/Cdh1 失活是由环素 E/Cdk2 启动并由 Emi1 稳定的一种快速,双稳定的切换.
- 在APC/Cdh1无活化之前施加的细胞应激会使细胞恢复静止状态;之后的应激不会.
结论:
- APC/Cdh1的失活是关键的承诺点,使细胞无法恢复静止状态.
- 这一发现澄清了细胞循环承诺的分子基础及其对疾病的影响.
- 了解这种转换可以了解癌症治疗的潜在治疗点.
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